Parathyroid growth and suppression in renal failure

In advanced uremia, parathyroid hormone (PTH) levels should be controlled at a moderately elevated level in order to promote normal bone turnover. As such, a certain degree of parathyroid hyperplasia has to be accepted. Uremia is associated with parathyroid growth. In experimental studies, proliferation of the parathyroid cells is induced by uremia and further promoted by hypocalcemia, phosphorus retention, and vitamin D deficiency. On the other hand, parathyroid cell proliferation might be arrested by treatment with a low-phosphate diet, vitamin D analogs, or calcimimetics. When established, parathyroid hyperplasia is poorly reversible. There exists no convincing evidence of programmed parathyroid cell death or apoptosis in hyperplastic parathyroid tissue or of involution of parathyroid hyperplasia. However, even considerable parathyroid hyperplasia can be controlled when the functional demand for increased PTH levels is removed by normalization of kidney function. Today, secondary hyperparathyroidism can be controlled in patients with long-term uremia in whom considerable parathyroid hyperplasia is to be expected. PTH levels can be suppressed in most uremic patients and this suppression can be maintained by continuous treatment with phosphate binders, vitamin D analogs, or calcimimetics. Thus modern therapy permits controlled development of parathyroid growth. When nonsuppressible secondary hyperparathyroidism is present, nodular hyperplasia with suppressed expression of the calcium-sensing receptor (CaR) and vitamin D receptor (VDR) has been found in most cases. An altered expression of some autocrine/paracrine factors has been demonstrated in the nodules. The altered quality of the parathyroid mass, and not only the increased parathyroid mass per se, might be responsible for uncontrollable hyperparathyroidism in uremia and after kidney transplantation.     

Cysts of the parathyroid glands. Apropos of 6 cases

Parathyroid cysts are rare lesions. Pathological examination distinguishes the "true" parathyroid cysts (non functional) most often present and cystic degeneration of a parathyroid adenoma (rare) with clinical or biochemical evidence of hyperparathyroidism. With the increased use of ultrasound and fine needle aspiration biopsies, the diagnosis of these cysts can be confirmed by an elevated parathyroid hormone (PTH) assay. The non-functioning parathyroid cysts can be successfully treated by total aspiration of the cyst fluid. Surgical exploration of all parathyroid glands is the treatment of choice for hyperparathyroidism. The different proposed etiologies for parathyroid cysts are discussed.     

甲状腺术中甲状旁腺识别技术的转化研究进展

甲状腺术中存在较高的甲状旁腺损伤或误切可能，如何原位保留甲状旁腺及其血供是甲状腺手术的难点之一，而实时识别是术中甲状旁腺保护的基础。近年来，甲状旁腺识别的临床转化研究获得了较大进展，主要集中在近红外光检测甲状旁腺的自发荧光、近红外光检测增强荧光和光学相干断层扫描成像技术的光学切片技术方面。甲状旁腺自发荧光能协助识别甲状旁腺，增强荧光能协助发现甲状旁腺并判断甲状旁腺血供是否受损、指导是否自体移植，而光学相干断层扫描成像技术能直接区分甲状旁腺和周围组织。甲状旁腺识别技术的转化研究进展将有助于甲状腺术中甲状旁腺的保护、减少损伤。     

Magnesium and the parathyroid

The serum levels of parathyroid hormone and magnesium depend on each other in a complex manner. The secretion of parathyroid hormone by the parathyroid is physiologically controlled by the serum calcium level, but magnesium can exert similar effects. While low levels of magnesium stimulate parathyroid hormone secretion, very low serum concentrations induce a paradoxical block. This block leads to clinically relevant hypocalcemia in severely hypomagnesiemic patients. The mechanism of this effect has recently been traced to an activation of the alpha-subunits of heterotrimeric G-proteins. This activation mimicks activation of the calcium sensing receptor and thus causes inhibition of parathyroid hormone secretion. In addition to the effects of magnesium on parathyroid hormone secretion, parathyroid hormone in turn regulates magnesium homeostasis by modulating renal magnesium reabsorption. The distal convoluted tubule is of crucial importance for parathyroid hormone-regulated magnesium homeostasis.     

Parathyroid autotransplantation during thyroidectomy

Permanent hypoparathyroidism is a debilitating morbidity following thyroidectomy, with a reported incidence of up to 43%. Apart from meticulous dissection to preserve parathyroid glands and their blood supply, parathyroid autotransplantation (PA) has been increasingly employed to preserve parathyroid function. The adoption of PA during thyroidectomy has been reported to be associated with a low incidence of permanent hypoparathyroidism. Biochemical function of parathyroid autografts can be demonstrated objectively by forearm reimplantation or during long-term follow up. The clearest indication for PA is for inadvertently removed or devascularized parathyroid glands during thyroid surgery. Other strategies, including routine autotransplantation of at least one parathyroid gland, can be considered, but is associated with a high incidence of transient hypocalcaemia. Apart from refinement in technique to facilitate graft success, a reliable way to assess overall parathyroid function or viability of individual parathyroid gland may assist in monitoring parathyroid function and selecting patients requiring this procedure to prevent permanent hypoparathyroidism.     

Factors that influence the assessment of parathyroid graft function

Autogenous parathyroid grafts are used in the treatment of primary and secondary parathyroid hyperplasia and for salvaging normal parathyroid glands removed during thyroid surgery. Placement of the autogenous grafts in the forearm may allow assessment of graft function by comparing the patient's background level of immunoreactive parathyroid hormone (iPTH) with the iPTH value in the antecubital vein above the parathyroid graft. Among patients who on clinical grounds seem to have functioning parathyroid tissue, significant iPTH gradients can be demonstrated in only approximately 80%. Several technical and clinical factors can prevent demonstration of an iPTH gradient in patients who in fact do have functioning parathyroid grafts. Hypercalcemia may suppress iPTH secretion. PTH secretion may be intermittent. High background levels of iPTH due to renal failure may transform a significant numerical gradient for iPTH into an insignificant percentage change in iPTH. It may be technically difficult to obtain blood from the particular vein bearing effluent from the parathyroid graft. The regional specificity of the iPTH assay employed may have an important influence on the magnitude of the apparent iPTH gradient. Knowledge of these factors should maximize the chance of documenting parathyroid graft function.     

The effect of cryopreservation on hormone secretion in vitro and morphology of human parathyroid tissue

The hormone secretion from human parathyroid tissue autografted after cryopreservation can fail frequently. In this study we examined the effects of the cryopreservation procedure on parathyroid hormone secretion in vitro and the viability of parathyroid cells to identify possible reasons for graft failure. Cryopreservation did not affect quantitative parathyroid hormone release from single-cell suspensions or its calcium-and magnesium-dependent regulatory mechanisms. However, morphometric analysis of thawed 1 mm3 graft particles showed various degrees of necrosis when compared with fresh grafts. Thus partial necrosis of cryopreserved tissue appears to contribute to poor transplantation results compared with immediate replantation of fresh parathyroid tissue. This limitation can be overcome by increasing the number of frozen graft particles used for autotransplantation. The percentage of viable cells should be accounted for by morphometric analysis and this factor used when calculating the number of graft particles employed.     

Parathyroid biopsy to facilitate the preservation of functional parathyroid tissue during thyroidectomy.

BACKGROUND: The preservation of viable parathyroid tissue, either by preserving parathyroid glands in situ with an intact blood supply or by autotransplantation, is an integral element of thyroid surgery. There is a general impression that nonviable parathyroid glands can be recognized on the basis of black or purple-black discoloration of the gland. We came to believe that this is not a reliable way to assess the viability of parathyroid glands because we observed that when we excised parathyroid glands (with the intention of reimplanting them) in situations where it was not feasible to preserve their blood supply, they did not become discolored. METHODS: To assess the status of the parathyroid blood supply, we performed incisional biopsies of suspected parathyroid glands during 14 consecutive thyroid operations (9 hemithyroidectomies, 1 completion thyroidectomy, 4 total thyroidectomies), and observed the biopsy site for evidence of active bleeding. RESULTS: Thirty-four of 36 possible parathyroid glands were histologically confirmed. Seventeen bled actively from the biopsy site and were preserved in situ. The other 17 were felt to be nonviable: 5 were severely discolored (black) and either no bleeding or minor venous oozing was seen when they were biopsied; 12 with normal coloration (3 were harvested prior to biopsy), did not bleed actively following an incisional biopsy. Parathyroid glands that were judged to be devascularized were autotransplanted into the sternocleidomastoid muscle. CONCLUSIONS: The absence of discoloration is not a reliable way to determine whether the parathyroid blood supply is intact. Biopsy of the parathyroid glands during thyroid surgery facilitates the identification of devascularized parathyroid glands that can be salvaged with autotransplantation.     

Molecular Genetics of Parathyroid Disease

Background  

Primary hyperparathyroidism (HPT) is often caused by a benign parathyroid tumor, adenoma; less commonly by multiglandular parathyroid disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple tumors require wider exploration to avoid recurrence and have increased risk for hereditary disease. Secondary HPT is a common complication of renal failure. Improved knowledge of the molecular background of parathyroid tumor development may help select patients for appropriate surgical treatment and can eventually provide new means of treatment. The present contribution summarizes more recent knowledge of parathyroid molecular genetics.     

Parathyroid cysts

Cystic neck masses may be accurately diagnosed by sonography, and some nonfunctioning parathyroid cysts can be cured by percutaneous aspiration. Primary hyperparathyroidism should be considered in all patients with cystic neck masses. Parathyroid cysts can often be recognized from the characteristics of the cyst fluid which is usually clear and colorless, contains elevated parathyroid hormone levels and normal or low thyroid hormone levels, and may contain parathyroid cells. Parathyroid cysts may be multiple; all four parathyroid glands should therefore be identified and appropriately removed or hyperparathyroidism may persist.     

Tactics and results of surgical treatment of hyperparathyroidism

Following a brief overview on parathyroid surgery, ontogenesis, anatomy and physiology of the parathyroids are described. Clinical symptoms and signs of hyperparathyroidism are as variable as the topography of parathyroid bodies may be. While parathyroid hyperfunction can easily be demonstrated by determination of serum calcium and parathyroid hormone levels, preoperative localization of adenoma or hyperplastic gland remains unsatisfactory in spite of great technical efforts. Therefore, the operative procedure has to be standardized and rational. Methylen blue staining of parathyroid bodies was proven to be helpful. Clinical results of 58 patients are presented.     

Parathyroid autotransplantation during thyroidectomy: documentation of graft function.

HYPOTHESIS: Biochemical function of normal parathyroid tissue grafted during thyroidectomy can be documented. DESIGN: An intervention study in which devascularized or inadvertently removed parathyroid glands are reimplanted in forearm muscle pockets during thyroidectomy. Postoperative serum parathyroid hormone levels were evaluated by venous sampling from both forearms on postoperative days 1, 3, 14, 28, 56, and 84. SETTING: Tertiary care teaching hospital. PATIENTS: Seven patients undergoing thyroidectomy at risk for postoperative hypocalcemia. RESULTS: A 1.5-fold gradient of parathyroid hormone measurements between grafted and nongrafted arms was demonstrated in all patients on postoperative day 28. A maximal parathyroid hormone gradient was reached on day 56, and biochemical function persisted in 6 patients on day 84. CONCLUSIONS: Biochemical function of parathyroid glands reimplanted during thyroidectomy can be demonstrated objectively. The application of parathyroid autotransplantation may preserve parathyroid function for inadvertently removed or devascularized parathyroid glands during thyroid surgery.     

甲状腺手术中荧光显像技术保护甲状旁腺的应用进展

在甲状腺手术中,甲状旁腺能否得到有效的保护将对患者的预后产生较大的影响。目前术中对甲状旁腺的保护方法多为肉眼识别,术者根据术中观察到的甲状旁腺的形态及血供情况,决定是否对其进行自体移植。然而,由于甲状旁腺在术中与周围脂肪及淋巴组织在形态和颜色上较为接近,这对肉眼的识别效果产生了很大的影响。因此,在甲状腺手术中急需一种帮助术者快速有效识别甲状旁腺的方法。近年来,荧光显像技术在甲状腺外科领域的应用成为研究热点,应用该技术在术中对甲状旁腺及其血供进行显像,为术中甲状旁腺的保护提供了一种新的方法。荧光显像技术可分为自体荧光显像（NIRAF）和外源性荧光显像两种方式,不同的荧光显像方式其所涉及的原理、运用的设备及术中实时显像的效果各不相同。目前NIRAF多用于术中对甲状旁腺的识别,该技术可以提高术者对甲状旁腺的识别率,但其显像效果受多种因素的影响,如患者的血钙浓度、甲状旁腺的位置及其周围组织情况等。外源性荧光显像依赖于荧光显像剂的应用,荧光显像剂主要包括吲哚菁绿（ICG）、低剂量亚甲蓝（MB）和5-氨基乙酰丙酸（5-ALA）。目前应用最广泛的荧光显像剂是ICG,当其与血中脂蛋白特异性结合后,在近红外光照射下可以对甲状旁腺及其周围血供进行显像,有助于术者对甲状旁腺进行识别,并判断其周围血供情况。随着甲状腺更多术式的不断开展,ICG近年来也逐渐在腔镜、达芬奇机器人手术中得以应用。这种方法的局限性在于其对甲状旁腺进行识别的结果存在着假阳性和假阴性的可能,且术者在对甲状旁腺周围的血供情况进行判断时,易受自身主观因素的影响。其他外源性荧光显像方法,如低剂量的MB和5-ALA的使用,尽管同样可以对甲状旁腺进行荧光显像,但因有文献报道其可引起多种不良反应,目前在临床上的应用并不广泛。由于目前荧光显像对于甲状旁腺的保护在国内外研究中仍处于初步阶段,不同技术其临床应用方法及效果都尚存争议。笔者结合目前国内外文献,就荧光显像技术与甲状旁腺保护的相关报道进行综述。     

Human parathyroid autotransplantation: proved function by radioimmunoassay of plasma parathyroid hormone.

The possibility of transplanting parathyroid gland fragments into accessible muscle as functioning autografts in the human being has been supported but unproved. During operations in the thyrocervical area, the parathyroid glands frequently are removed, either intentionally or inadvertently. We have had occasion to transplant slices of parathyroid glands in five instances; four parathyroid glands were proved to be normal, and a benign adenoma appeared in the fifth. The parathyroid gland was positioned in a muscular bed in the patient's forearm. Plasma parathyroid hormone (PTH) measurements by radioimmunoassay were made from the implant venous effluent. The venous outflow from the contralateral arm was used for control. We have concluded that parathyroid tissue can be transplanted, does function, and might be capable of providing calcium homeostasis.     

Management of primary hyperthyroidism: toward minimal access surgery

Fifteen years ago, bilateral exploration of the neck was dogma in parathyroid surgery. Now, less invasive procedures can be used to target lesions identified by new tests such as dual-phase Sestamibi scanning or intraoperative documentation of parathyroid hormone (PTH) level changes after removal of a parathyroid gland. A hand-held gamma probe can be used for intraoperative detection of high-uptake lesions, and video-assisted endoscopic surgery has been used successfully. With these new techniques, surgical exploration can be confined to one side of the neck through smaller incisions associated with better cosmetic results. The operating time is reduced, and in some cases the procedure can be done under local anesthesia. The objective of this article is to describe recent changes in the management of parathyroid adenoma requiring surgery.     

Recurrent hyperparathyroidism due to peroperative seeding of neoplastic or hyperplastic parathyroid tissue. Case report

The clinical course and histologic characteristics of recurrent hyperparathyroidism due possibly to peroperative seeding of parathyroid cells are described in four cases--two of parathyroid adenoma, one of parathyroid hyperplasia associated with multiple endocrine neoplasia type 1 and one of parathyroid carcinoma. The observations underline the necessity for careful handling of parathyroid lesions during extirpation, and that the multiple nodules of implanted parathyroid tissue can be curatively excised in some cases.     

Intrathymic parathyroid adenoma

Intrathymic parathyroid adenoma is a rare cause of persistent primary hyperparathyroidism. We encountered a case of intrathymic parathyroid adenoma, detected by computed tomographic scan and confirmed by Technetium-99 (Tc-99) Sestamibi scan and histology. The surgical approach included a median sternotomy and a large intrathymic parathyroid adenoma was identified and excised through the sternotomy. In this case, Tc-99 Sestamibi scan successfully localized a persistant abnormal tracer uptake in the mediastinum suggestive of mediastinal parathyroid adenoma. Although not recommended for routine preoperative evaluation, scintigraphy can be useful in the preoperative localization of ectopic parathyroid adenomas.     

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium.

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium. In this study, the parathyroid response to the correction of acidosis in eight hemodialysis patients was determined by performing dynamic assessment of parathyroid function before and after the correction of acidosis. The parathyroid response to intravenous calcitriol before and after the correction of acidosis was also assessed. After optimal correction of acidosis, there were no significant changes in blood pH, ionized calcium, phosphate, or alkaline phosphatase values, but the level of venous total CO2 increased significantly. Parathyroid hormone/ionized calcium curves were displaced downward after correction of acidosis, but not after the administration of intravenous calcitriol. The correction of metabolic acidosis in hemodialysis patients with secondary hyperparathyroidism can suppress parathyroid hormone secretion by increasing the sensitivity of the parathyroid glands to ionized calcium.     

Parathyroid Ultrasonography in Renal Secondary Hyperparathyroidism: An Overlooked and Useful Procedure

In secondary hyperparathyroidism (SHPT), ultrasonography (US) can accurately define the size and structure of parathyroid glands as well as differentiate diffuse and nodular hyperplasia. US may be also useful to predict the response of SHPT to vitamin D analogs and cinacalcet and to assess for regression of parathyroid glands hyperplasia by measurement of parathyroid gland volume. There is increasing evidence that US can potentially identify patients who will benefit from prompt surgical intervention. Therefore, US should be part of the diagnostic armamentarium in the treatment of SHPT in the daily clinical practice.     

Familial form of primary cancer of the parathyroid glands. A disease entity or incidental association?]

Three cases of parathyroid neoplasms in familial hyperparathyroidism are reported. There were not associated with other endocrine glands or parathyroid glands lesions. Parathyroid gland carcinoma was diagnosed in 2 cases. Review of 7 cases of familial parathyroid carcinoma, diagnosed in 5 different families and issued from the literature, indicates that it can be associated to multiple endocrine neoplasia or other parathyroid lesions. The familial parathyroid carcinoma entity needs further studies before to be fully recognised.